Thankfully, I already have a leg up on that one.  Back at SLU, I had the good fortune of getting to teach in “Drugs We Use and Abuse,” a course run by the graduate students of the Pharm/Phys Department.  It is team-taught each Fall to around 50 non-majors (e.g. Business majors, History majors, etc.) and generally centers around…well…just what it sounds like.  If you ever wanted to learn what meth, cocaine, opiates, depressants and caffeine do to your body, then this is the class for you.  I taught in it for 3 years: I was a section director for 2 of those years and course director for 1 year.  The experience was very good, so much that I decided I want to do it full-time as a career: teach at the undergraduate level.

When I took the position here at the University of Iowa, I asked my mentor if it would be alright for me to continue teaching occasionally alongside the rest of the research I’m doing.  He was kind enough to allow it (if anything, he was excited that I’d take a few lectures off his hands).  This October, I’ll be teaching two classes of Advanced Toxicology, one talking about neurotransmission and the other talking about neurotoxic agents (e.g. cocaine, methamphetamine and ecstasy).  Both of these subjects are within my proverbial wheelhouse, so they shouldn’t take up all that much preparation time.  That, and I have the previous year’s lectures in a Powerpoint file to help me throw something together.  While Drugs We Use and Abuse was directed at non-major undergraduates, this class is for graduate students and there are only 12 in the class, so the dynamic will be quite a bit different than what I’m used to.

I will likely get the opportunity to teach in the Spring as well.  That course is in our department, Medicinal Chemistry and Natural Products, and is also targeted at graduate students (and will likely be just as small, if not smaller).  Not sure when we’ll get that going, but it probably won’t be until January, knowing how things go around here.

Either way, I think I’m doing a reasonably decent job at preparing for what’s ahead, with regards to that whole “career” thing.  At the very least, getting to add a few “guest lecturer” points on my CV is always a welcome addition.

And maybe I’ll even have a little fun doing it.  :-)

One of my favorite video game genres is the “Real Time Strategy” game, or “RTS.”  In such a game, you generate resources in order to build units that the allow you to conquer the other player.  Starcraft II is, perhaps, the most recent example of such a game, and one I’ve been playing a great deal of recently, however the Age of Empires series is, perhaps, best-suited for explaining more clearly.  In an RTS like Age of Empires, you start the game with a few units (Villagers) that harvests resources for you, like wood, food, stone and gold.  These four resources help you to produce other Villagers, but also Military units.  When you’re starting out in the Dark Ages, you primarily need food and wood for “Clubmen,” but as you advance toward “Swordsmen,” you need more diverse resources like gold.

These games are generally part of a larger game mechanic called “resource management.”  Basically, you begin a given game with a finite amount of resources and you choose how to spend those resources.  Some of them should go to more resource-generating (e.g. investments), while other resources should go toward the ultimate goal of the game.  It’s up to the player to decide to what degree they go in either direction.  If you want to win quickly, then you pour more resources into building military units so you can take out the other player.  If you want to “tech up” to a more stable position, but take longer doing it, you pour those resources into investments.

As I said, I’ve always liked this kind of game.  But I’ve never been terribly good at it in real life.

Brooke and I have never made huge amount of money, but the move to Iowa cost us a great deal.  Brooke was unemployed for the first 3 months of living here, and she’s still only been able to get work part-time (but that’s going to steadily increase).  That combined with the fact that we have a baby now means that our collective (limited) resources have been directed in other avenues than what we are used to.  Child care alone is a ridiculous, but necessary, cost.  Therefore, we’ve been doing our best to maximize our available resources as best as possible.  With various payments that one has to car loans, student loans, life/auto insurance, etc., that only leaves a relatively small percentage of cash that you can adjust for whatever purpose is required.

A few summers ago, we started with helping limit our energy costs by getting a single-room A/C unit for our bedroom.  That helped save us $100 in a single summer, paying for the A/C unit itself.  We’ve been using it in our house in Iowa now, helping to limit the excess cost of cooling a much larger space than we were dealing with in St. Louis by only cooling our bedroom(s) at night, as opposed to having our central A/C running too heavily.  Thankfully, Iowa summers are substantially cooler than St. Louis summers, and the house is in the shade enough that it rarely heats up to a significant degree.  We’re already talking about ways to limit the amount of propane we’ll use in the relatively harsh Iowa winters, trying to defend against the northwest wind by insulating specific windows.  We’ll probably spend more time upstairs, as the heat will collect there.  We’ll probably try keeping the house cooler than we had it in St. Louis, as well.

We’re also trying to limit travel to some extent.  When we can take Brooke’s Scion xA on longer trips, we’ll take it (37 mpg), but when we need a larger vehicle, we’ll have to use the Sportage (27 mpg).  I’m driving the Sportage to and from work every day and, on those trips, I’m doing my best to stay around 65 mph, as an engine runs most efficiently within that range.  Doing so, I’ve been able to help limit my gas costs to a reasonable degree.  I’ve also started getting up earlier, getting to work around 7:00 am and leaving around 4:00 pm, thereby allowing me to miss the traffic that frequently causes me to speed around people.

Brooke has done an excellent job over the summer growing vegetables and canning them for later months.  We’ve been able to save a pretty decent amount of money on food already, but those savings will continue on into the winter months.  So far, Brooke hasn’t had to buy much solid food for Meg, either, as the carrots and squash she’s been eating were grown in our garden.  Brooke froze down more of it so she can make more in the next few weeks.  As Brooke already posted about the cloth diapers, we’ve already saved a pretty large amount of money over disposables.  Otherwise, we still shop at Aldi, as always, but are making a more concerted effort to limit the “extras” (although, Brooke has already demanded that her ice cream allotment not be limited).

Our entertainment costs have dropped dramatically, as we don’t have cable anymore and our internet connection is fast enough that we can Netflix or stream everything we want.  I’ve seen one movie in theaters this summer and have decreased the number of games I’ve purchased, as well.  We also aren’t going out to eat as often, partially because we have to hold Meg and would rather have her in a high chair or something (which she isn’t…quite…ready…for…).

We’re still looking for improvements, but I think this is a helpful, albeit stressful, experience.  As in RTS games, if you build up your resource-generating units early on, you get a strong economy that can then provide you with better military units later in the game, allowing you to conquer and win.  It takes keen resource management to do this, as you have to be very, very efficient with the military units you do build early in the game, while instead putting those resources into things that can help you later on.

Let’s hope we learn something now, so that we’re prepared for later stages of the game.

As I’ve mentioned…oh…countless times, I became interested in my chosen field primarily because of a class titled “Psychopharmacology,” offered by the Psychology Department at Truman.  As the name suggests, the class primarily focused on how drugs modify an individual’s mental state, whether it’s an illicit drug that changes the way you act (e.g. methamphetamine), or one that’s used to help you cope as you carry out your day (e.g. diazepam [Valium]).

Back in June, I posted about Pharmacology, the study of how a drug acts within an organism.  One thing I discussed, but did not elaborate on, was that many drugs function at receptors, and the modification of these receptors is what gives you the desired effect of said drug.  However, in order to understand how these receptors actually do something to your body, you need to understand the basics of how neurotransmission works.

Basically, neurotransmission is a signal sent between two specialized cells called neurons.  These cells make up a large portion of the brain (i.e. there are other cell types, including astroglia and microglia) and provide all the processing power you need to carry on with whatever task you wish.  Therefore, if you want to modify something about that task, these are important cells to consider and/or target with a drug.  Neurons take advantage of channels in their membranes that allow selective transfer of ions like sodium, potassium, chloride and calcium.  When these ions cross the membrane from outside the neuron to the inside (or vice versa), an electrical charge is produced.  These channels open and close selectively to allow certain things through, and keep other things out.  For example, sodium channels in neurons typically allow sodium into the cell, while potassium channels tend to allow potassium to leave the cell.

Many of the receptors that drugs are targeted toward are channels, or the drug-targeted receptors somehow affect the ability of channels to open or close.  Therefore, if you can target your drug toward a specific channel, you can keep it open longer, or close it sooner, allowing you to affect whether a neuron is able to continue propagating its signal.

So, the electrical signal caused by transfer of ions across a neuron’s cell membrane (or “action potential“) travels down the neuron, from end to end.  On one end is the “cell body” (or “soma”) and on the other end is the “axon terminal.”  The electrical signal always goes from the cell body to the axon terminal.  The cell body is covered in “dendrites,” outcroppings of the cell that receive a signal from another neuron’s axon terminal.  Therefore, typically, (1) a signal will start at the dendrites; (2) travel down the axon; (3) trigger a set of events in the axon terminal resulting in (4) the release of a neurotransmitter that (5) crosses the synapse until it reaches another dendrite and (1) starts the process over again.

What happens between the axon and the dendrite can best be described by this image, stolen from Wikipedia:

Neurotransmitters are packaged in “vesicles” that are directed to release their contents into the synaptic cleft where they travel across the cleft to the opposing dendrite, setting off a similar cascade in the next neuron.  There are also “reuptake transporters” in the cleft to help remove excess neurotransmitter, so you don’t have that opposing neuron continuing to fire too long.

Examples of neurotransmitters include dopamine, adrenaline (epinephrine), acetylcholine, nicotine and serotonin.

Now, you probably recognize a few of those neurotransmitters, right?  For example, you probably know that serotonin happens to be very important to your mood.  If you don’t have serotonin, you tend to get depressed.  So what can you do to help combat this deficiency?  Try taking an SSRI (selective serotonin reuptake inhibitor).  That drug targets the “reuptake transporter” in the cleft, allowing the serotonin you’re already making to stay in the cleft longer, helping to activate those neurons to keep your mood a bit happier.

You’d use an SSRI to help serotonin to reach its target neuronal receptors, thereby allowing for increased signal propagation through neurons.  But what if you want to limit propagation of signals, for example, in the case of an epileptic seizure when neurons are firing uncontrollably?  You can use a depressant like carbamazepine.  This drug targets channels and modifies them in such a way that the electrical signal (“action potential“) being sent down the axon is limited, or “depressed.”  It prevents the signal from continuing and, therefore, less (or no) neurotransmitter is released into the synapse.  That same drug can be used to help treat the manic symptoms of bipolar disorder, as well.

So, all of these principles are taken into account (as well as countless others…) when looking for drug targets, and when doctors are prescribing medications.  This is why you can have so many complications when you are prescribed a cocktail of medications, especially when you get older.  If you are taking, say, 10 different medications per day, prescribed by different doctors, it is easy for at least one of those drugs to counteract the effects of another.  There are many factors to consider when prescribing or taking these kinds of medications, as they have effects all over the body.  One simple example is methamphetamine.  This drug targets that reuptake transporter, much like an SSRI does, but it (1) does so for a class of neurotransmitters called catecholamines, and (2) reverses the transporter, rather than blocks it.  The class of catecholamines include dopamine and adrenaline.  So, if you take methamphetamine, you will be increasing the amount of dopamine and adrenaline in your body, not just your brain.  Your heart races because of the adrenaline, and the psychological effects occur because of the dopamine (including its addictive qualities).

In summary, neurotransmission is pretty complicated, but its basics are understandable.  The take-home concepts are:

• Neurons are responsible for “processing” in your brain, and they use electrical and chemical signals to communicate with each other
• Many drugs that affect your psychology target the ability of neurotransmitters to “continue the signal” from neuron to neuron
• Some drugs affect more than one aspect of neurotransmission, and in more than one location

Meg is breastfed and was exclusively (except for about an ounce of formula in the hospital because I was freaking out that she was hungry…I know better now) until she started eating rice cereal at 4 months. There’s another post coming about how that’s going for another time. I still continue to nurse and to pump while she is at daycare about 5-6 times each day, which I’m guessing gets Meg about 28 ounces of breastmilk a day, which should be plenty. I’m starting to think about weaning her to a combination of stored breastmilk and formula from a bottle in the next month or so, mostly because my work schedule is complicated and there’s not always time or a place for me to pump when I need to, and because I’m starting to feel like I’ve done my job in this arena. I have a feeling that weaning will go slowly to ease the hormonal and therefore emotional toll it will take on both of us (or all of us, really because Andy will have to deal with it, too).

I think to breastfeed or not is a very personal decision, just like I think most parenting decisions should be. It’s super easy to start thinking that your way of doing things is better than anyone else’s, and why this is true for each parent’s situation, I’m trying really hard to not worry what other people think of what I’m doing with my job and at the same time not judge other parents for their decisions.

That being said, when I was looking at how much money we’ve saved my cloth diapering, Andy was also interested in how much money we’ve saved by not buying formula. Here are the CDC’s statistics on the numbers of infants in the United States who were breastfed in 2006:
* 73.9% were ever breastfed
* 43.4% were still breastfeeding at 6 months of age
* 22.7% were breastfeeding at 1 year of age
* 33.1% were exclusively breastfed through 3 months of age
* 13.6% were exclusively breastfed through 6 months of age
So, obviously, most babies are being breastfed at least some, so this number isn’t this high unless a baby has only ever had formula. But, for a basic, name brand formula, for the first 6 months of life, you will have spent $717.93 to feed a baby. Breastfeeding is absolutely free!! In our case, since I have a pump and the necessary accessories for storing and feeding pumped breastmilk, the net savings is about $400.00. That’s pretty good from a purely monetary perspective, if you ask me (and I know you didn’t, but whatever…)!

How we’re cloth diapering was discussed here, but not the costs. A lot of people will say that, in the end, the costs associated with cloth diapering doesn’t really save a lot over disposables, while others say that you break even with your first child and the savings come with subsequent children. I contend that disposable diapers are WAY more expensive than cloth. And, from my experience, I’d also say that anything that is cheap is also good for the Earth (hanging clothes on the clothesline, gardening, driving a high gas mileage car…), so we’re doing our part!

I also added in 20% of the cost of our new washing machine because we probably wouldn’t have bought such a nice one if we weren’t washing diapers 2-3 times each week. The amount of electricity used seems fair, as it also includes water since we have a well and sewage since we have a septic tank. We do not currently have trash removal, but if we used disposable diapers, we would have to pay for that as well!

The ongoing costs of cloth diapering from this point will include a few more covers as Meg gets bigger, but the current ones should fit her until she’s at least 18 pounds, and electricity. Our electric bill may increase a little in the winter when I can’t hang the diapers out to dry as often, but I really don’t very often now anyway because they have to hang outside all day and I usually need the clothesline space if it’s a Saturday and I’m doing lots of other laundry.

I totally paid for those boots just in cloth diapering the last 6 months ($186.00 saved!!!!), but now I’m looking for other ways that Andy can thank me for being so frugal! Up next, canning, canning, canning.

As I’ve stated before, I’m a “Postdoctoral Research Scholar” in the College of Pharmacy at the University of Iowa.  A “Postdoc,” as we’re commonly referred to, could be equated with a medical doctor’s “Residency” period.  At this point in the career, you are above a Graduate Student (i.e. no longer taking classes), but you’re still below a full Faculty Member (i.e. no responsibilities with committees, teaching, etc.).  Basically, you have more responsibility and freedom than you did as a Grad Student, but you still report to a mentor for training and guidance.  I have been adjusting to this dynamic over the past three months, but it will probably become more apparent as the school year starts and the graduate students in the lab start attending various functions that I’m not required to attend anymore.

Speaking of which, the other students in the lab are cool.  They certainly aren’t like what I experienced at Saint Louis University (no alcohol allowed on campus…stupid public schools… ), but they are a dedicated bunch that do good science.  This is also a larger lab environment than I became accustomed to at SLU, with 4 graduate students and a lab manager (and now a postdoc) in this lab alone, plus all of the other students in the other labs we work with.  The grad students in our lab are working on related, yet different, aspects of Parkinson’s disease, ranging from the effects of neurotoxins on PD-like symptoms to protein binding to dopamine metabolism.  One thing I’ve noticed is that this lab is much more Chemistry oriented than anything we had at SLU.  Considering that I haven’t taken a Chemistry course in over 5 years, I’m having to remind myself and/or re-learn some basic concepts that I haven’t had to use since then.

However, that’s kinda the point of a postdoc.  The general rule of thumb in choosing an appropriate postdoc position is to a). use techniques you already know in a different scientific field, or b). stay in the same scientific field but learn completely new techniques.  I would fit into the latter category, as I’m still working in PD research, but I’m using Chemistry much more than I did in Grad School.  The ability to use mass spectrometry as an analytical technique is especially exciting in that it’s something I’ve wanted to learn more about since Undergrad, but haven’t had access to the equipment to learn on.  Now I do, and I have a variety of scientific questions built up in my head over the past few years of things to look at.

I have just started working on a grant.  The National Institutes of Health (NIH) is the primary government entity that provides scientific research funding, and they offer an F32 grant for Postdocs designed to help defray the cost of their employment, but also provide the funds for you to train in things you don’t know much about.  The application is due in December, so I’ve got some time, but right now I’m working on getting some preliminary data to include in the 6 page research design portion (6 pages is very, very little…I could write 20 pages today on the subject, but figuring out what is important and what isn’t will be the challenge).  The NIH has a relatively high fund rate for F32s, but the award is by no means guaranteed.  I’ve never submitted one before, but I’m going to do my best to write the best one I can.

Regardless, the lab itself is a good learning environment and I’m learning more and more about my co-workers every day.  It took awhile to figure out all of their “inner-workings” (i.e. who will take to my sarcastic personality and who won’t…), but I’m getting closer.  The science itself is very interesting and I feel like I’m learning, hopefully preparing myself for what lies ahead.

I’ve had magazine subscriptions of various types for years now, beginning with Boy’s Life (the Boy Scout magazine…) and various computer game mags, and then eventually to Popular Science and Consumer Reports.  However, in recent years, there have been a number of news stories discussing “The Death of Print Media,” including magazines and newspapers, primarily.  This is mostly due to the Internet and its ability to get you the same information much, much faster than a weekly or monthly periodical can, and cheaper as well.

Recently, however, certain magazines have begun to toy with digital versions of their material.  These are magazines that have either dropped in subscribers to a substantial degree, or have already folded for a variety of reasons.  For example, while TIME Magazine is apparently weathering the storm, Newsweek just got hammered by a drop in subscribers to the point where they were looking for a buyer.  Gourmet Magazine shipped its final issue at the end of 2009.  On the gaming side, Electronic Gaming Monthly was shuttered at the beginning of 2009.

Some magazines have gotten around this problem by increasing the quality of their material.  Edge Magazine, a gaming periodical in Europe, has proven to be successful by starting to use thicker, glossy paper, raising the perceived value of their product over their competitors.  The magazine just looks good sitting on your table, with its larger paper and glossy images.  It’s the kind of thing you want to keep on your coffee table, as opposed to other magazines that are constantly including more and more ads and thinner, newspaper-like print.  They also limit the number of individual magazines they produce, only making enough to send to subscribers (all over the world…) and keep a limited number on news stands.  This helps keep their costs down, rather than making more magazines than the public will buy.

Alternatively, some of the aforementioned publications are going digital…and in a big way.  The advent of the iPad has allowed Newsweek and Sports Illustrated (amongst others) to get weekly content to readers on-the-go very cheaply, effectively replicating web-based content in a magazine-oriented format.  You can turn the pages as you would with a book, but now making a touch-based gesture on your iPad screen.  The images are very colorful, print easy-to-read, and perhaps most important of all, they can now include hyperlinks and video content that you can’t with a regular magazine.  Recently, it was also  announced that Gourmet Magazine was relaunching as Gourmet Live, also releasing on iPad (announcement video below).

Similarly, Electronic Gaming Monthly was bought out by the guy that started the magazine in the first place back in the 90s and relaunched in both print and digital formats.  For a demo, click this link and it will take you to a freely available copy of the magazine (pictured above) so you can see what it looks and feels like (and you should “Experience in Full Screen”).  While you may not be interested in video games in the least, at least you’ll get an idea of what is possible through digital distribution of magazines.  EGM also has an iPad version, but this particular example is representative of what you can experience in any web browser.

So, is “print dead?”  Probably not, but it’s definitely evolving.  Everything I’ve heard suggests that print journalism majors are finding it difficult to get jobs once they graduate from college, as many newspapers and magazines are scaling back, if not shutting their doors.  The primary hurdle appears to be advertising, as very, very few companies have been able to make it with their large-scale operations solely on the advertising revenues of web-based content.  The New York Times tried unsuccessfully to require subscriptions on portions of their website years ago (and they’re trying again in 2011), but our culture tends to shun pay-for content on the internet, at least with regards to news.  There are just so many blogs available, or other free sites, that get you the same information for no money at all.

Personally, I’m on board with a model like Edge or EGM is using, one where they produce magazines in limited quantity for the people that want it, but otherwise provide digital versions for those that don’t care either way.  Honestly, I still read everything on blogs and only go to the “primary source” sites when linked there.  I like the way EGM has set up their content, but I think I’d rather have an iPad or some other similar device for that purpose, rather than use my heavier and more unwieldy laptop (imagine sitting in bed and reading…would you rather hold your laptop or your iPad?).

I think a lot of people value the content they get from magazines and newspapers, as the journalists that write them get access to news and information they otherwise can’t.  Bloggers generally don’t have correspondents in Afghanistan, so they rely on organizations like NPR and the Associated Press to gather the news, and bloggers just put their own spin on it and spread it as well.  We still need primary news sources to survive this transition from “old media” to “new media!”

So, my 2003 Hyundai Elantra served us well, but a). had 107,000 mi on it; b). needed extensive brake work; and c). needed new tires.  Rather than drop $1000 on various repairs on a car with that many miles on it, and a car that probably wouldn’t perform well in the Iowa winters, we were considering getting something a tad bit newer.

We’d been discussing a 2010 Subaru Forester for awhile, largely because they hold their value substantially longer than other vehicles, they’re reliable, and they have all-wheel drive standard.  However, considering the value of our trade-in (which wasn’t much…), it just wasn’t going to be feasible anytime soon…  Therefore, we expanded our options to look for something closer to what we were paying on our Elantra (i.e. relatively little, compared to what it would be with the Subaru…).  The options are rather limited with those kinds of restrictions, but we were able to find this 2006 Kia Sportage at a local Ford dealer.  It had a few more miles on it than we were initially considering, and it didn’t have 4WD or anything, but it did improve road clearance over our Elantra (let alone Brooke’s Scion xA) and it had more safety features than the Elantra did (e.g. ABS, traction control, ESC, curtain airbags).  Honestly, for the number of miles on the car, I’m shocked the exterior of the car is as pristine as it is. To be fair, the interior isn’t too shabby, either.

Anyway, we’ve got another car now.  This one should get us through winters here, and will certainly be more comfortable traveling on the gravel roads of Iowa (and there are many…).  I’m pleased with it and think it’ll serve us well.  Maybe it’ll end up being Meg’s first car…

I also picked the first several-tomatoes-at-a-time crop today.  Andy took this shot of some of them in the window sill ripening a little more.  I’ll process them tomorrow, hopefully.

And, for your viewing pleasure, here’s Meg, in her bouncy seat where she spends a lot of time while I’m cooking and whatnot!  You can tell how excited she is about the BLTs we had for dinner.

My postdoctoral fellowship here at the University of Iowa still involves research on the mechanisms by which Parkinson’s disease progresses, much like my research at Saint Louis University, but I’m employing different techniques.  In an effort to explain those techniques, I’m going to try outlining them here, as it’s a technique that’s “tossed around” on shows like “CSI:” on an almost weekly basis.

Mass Spectrometry is a technology developed over 100 years ago and has been employed by researchers for much of that time.  The high cost of procuring one of these instruments (easily in the $10,000s, if not approaching $100,000+) makes them somewhat difficult to find in the undergraduate setting, and sometimes difficult to find in graduate schools.  Larger institutions, such as the University of Iowa, will have a few of them, but more than likely, you’ll have to share the instrument with quite a few others, not-so-patiently waiting their turn.

The instrument I’m using is called an LCMS-IT-TOF, pictured above.  The acronym stands for “liquid chromatography mass spectrometer – ion trap – time of flight.”  Each section of the acronym represents a distinct component of the mass spectrometer: there are different components that can be inserted to achieve similar analytical results in a different fashion.  Some components are better for some types of analyses, while other components are better for others.

But, in keeping this relatively simple, I won’t go into it each part.  Feel free to check out the Wikipedia article on the subject if you really want to know more about it, but basically, a mass spectrometer is divided into three primary components:

• A source
• A mass analyzer
• A detector

The “source” effectively destroys whatever you’re wanting to look at.  There are a variety of different sources one can have in their configuration (e.g. MALDI, ESI, ACPI, etc.) In my case, let’s say you have a protein you want to investigate.  The mass analyzer can look at it, but the nature of the type of data it provides makes it much easier to break the protein up into smaller bits first.  Therefore, the source breaks up your relatively large molecule of interest (such as the protein in our example) into smaller, more manageable pieces.  As with many other things, taking things in “baby steps” is much easier to deal with.

The “mass analyzer” is necessary to help with sorting of all those small, manageable pieces.  Think of this process like a box of cereal (I know, right?). Specifically, Frosted Mini-Wheats.  When you open the box, you’ll notice that there are mostly fully-formed Mini-Wheats at the top of the box.  As you continue on toward the bottom, you’ll start seeing some smaller pieces, some that may have split in half, for example.  And at the bottom of the box, you’ll see all the individual wheat fibers and sugar frosting.  The same premise holds for a mass analyzer.  All those pieces of protein broken up by the source are in different sizes, and the mass analyzer helps sort them out in such a way that the small pieces, medium pieces, and the large pieces are all separated.  As with the source, there are many different types of mass analyzers (e.g. TOF, IT, Quadrupole, etc.) used to carry out this work, depending on what you’re looking at.

The “detector” is the piece that really gives us the information we want.  After those bits of sample are sorted, they each hit the detector one at a time and the detector tells us what the mass is, typically by actually reading the electrical charge of the sample.  Typically, the source (sometimes referred to as an “ionization source”) introduces a charge to each piece of the sample, allowing for the detector to…um…detect them.  :-)

So, how is my work fitting into this?  Our lab is interested in how a particular molecule, 3,4-dihydroxyphenylaldehyde (DOPAL) may be involved in Parkinson’s disease.  DOPAL is a metabolite of dopamine, the neurotransmitter necessary in order for you to make voluntary movements.  When you run out of dopamine (or the cells that produce it, in the region of the brain where you need it), you get Parkinson’s disease.  Dopamine is present in those cells, which therefore means DOPAL is present, too.  DOPAL is an aldehyde, which means, on a chemical level, it can bind with other molecules relatively easily.  What we want to know is whether DOPAL may bind to proteins within those cells.  This may matter because cells tend to function in certain ways, and if their individual parts (e.g. DNA, organelles, proteins, etc.) get modified somehow, they won’t work properly and, subsequently, the cell will kill itself to prevent further damage to surrounding cells and tissues.

We want to see whether DOPAL binds to any proteins.  If we can find proteins that DOPAL binds to, and if we know what those proteins do inside a cell, then we may be able to a). protect them against DOPAL’s binding, or b). develop drug targets toward those proteins to help prevent them from causing death of the cell.

How does mass spectrometry fit into this equation?  Back to our early example of a protein being introduced into a mass spectrometer.  The instrument will tell us how much a protein weighs on a molecular level.  We also know how much a single molecule of DOPAL weighs.  We can, thus, use a mass spectrometer to see whether the mass of a protein increases when DOPAL is present.  If that occurs, we can show that DOPAL has bound to the protein.  We can also get information as to where on the protein DOPAL bound, or how much DOPAL bound to the protein, and so on.

In the image above (upper left), you can see some vertical lines we refer to as “peaks.”  Each peak represents a single mass of a given protein or molecule.  You can then take that peak and “fragment” it into smaller peaks.  You can do this multiple times (e.g. MS, MS2, MS3 and so on…).  Fragmentation patterns give you an idea as to what makes up a complex molecule.  For example, if you went from MS to MS2 and had a loss of 18, you could say that you lost a water molecule during fragmentation (O=16, H=1…H2O=18).  In the case of DOPAL, we would see an increase in mass (and a shift of the peak) of 151, depending on how DOPAL bound to our protein of interest.

So, basically, that’s what I’m doing in the lab.  There’s quite a bit more to the story than this, but I think I’ve simplified the concepts to a mostly understandable level.

Probably not, though.  :-)